NIVOPOSTOP (GORTEC 2018-01): A phase III randomized trial of adjuvant nivolumab added to radio-chemotherapy in patients with resected head and neck squamous cell carcinoma at high risk of relapse.

NIVOPOSTOP is an international randomized, open-label Phase 3 trial (NCT03576417). Main inclusion criteria were patients < 75 years, ECOG PS 0-1, with resected LA-SCCHN of the oral cavity, oropharynx (OPC), hypopharynx or larynx at high-risk of relapse defined by presence of nodal extra capsular extension and/or positive tumor margins, ≥4 nodal involvements, multiple peri-neural invasion. The primary endpoint was Disease Free Survival (DFS); key secondary endpoints include overall survival (OS) and safety. Patients were randomized 1:1 after surgery to receive Arm A SOC 66 Gy RT and cisplatin (100 mg/m2 every 3 weeks (Q3W) for three cycles) or Arm B NIVO 240 mg, followed by SOC CRT with 3 cycles of NIVO 360 mg Q3W, and followed by 6 cycles of NIVO 480 mg Q4W. Treatment allocation was done by minimization for centers and p16 status. To detect a HR of events of 0.65 at 2-sided alpha error 0.05 and power 90%, 230 events were required. Analysis was performed when this required number of events was reached (cutoff date April 30, 2024).

A total of 680 patients were randomized. DFS analysis was based on 666 patients randomized before the cutoff date (334 in Arm A vs 332 in Arm B; intent-to-treat analysis) and 252 events at a median follow-up of 30.3 months (IQR 16.0; 44.9). Baseline characteristics were balanced between both arms. DFS was significantly improved across PD-L1 all-comers with adjuvant NIVO + CRT vs. CRT alone (HR 0.76 (95% CI, 0.60-0.98); stratified log rank test p value = 0.034). The 3-year DFS was 52.5% (95% CI, 46.2-58.4%) with CRT vs. 63.1% (57-68.7%) with NIVO + CRT. The analysis of OS will occur when the required number of deaths will be reached (currently 158 and required 283 deaths). The compliance with CRT was similar in both arms. Safety analysis up to 9 months after CRT was based on patients who received at least one administration of treatment. Patients experiencing grade 4 adverse events were less frequent in patients receiving CRT vs. NIVO + CRT (5.6% vs. 13.1% until 100 days after CRT and then 0% vs. 1.2% up to 9 months), and treatment related deaths occurred in 0.7% and 0.6% of patients, respectively.